The research of this laboratory remains focused on the regulation of cholesterol homeostasis in the human body in health and disease. To this end we continue to develop and to refine non-invasive methods for measuring the key determinants of that regulation: absorption, synthesis, transfer into and out of tissues, conversion to bile acids, and finally, excretion. We rely heavily on the General Clinical Research Center in the Hospital for these metabolic ward experiments, but the progress made in the last year now permits us to extend some of these studies into larger out-patient use. In the coming year we intend to explore further the uses and limitations of the new method developed here for measuring cholesterol synthesis rates in the unsteady metabolic state. In addition, we are developing rapid methods for measuring cholesterol absorption rates in absolute terms in out-patients in order, by linking synthesis and absorption data, to evaluate the perfection of feedback control of cholesterol synthesis in individual patients with hyperlipidemia. Tissue culture work with human skin fibroblasts will continue, in search of an explanation for the hyperglyceridemia seen in families with combined hyperlipidemia. In addition, work has been initiated with human leucocytes: conversion rates of acetate to cholesterol and fatty acid esters, and assays of HMG-CoA-reductase activity. These in vitro studies of living cell systems will be carried out in parallel with metabolic studies of cholesterol homeostasis of the donor himself, in order to search for correlations that may lead to simpler methods of identifying individual pathogenetic defects in outpatients with various forms of hyperlipidemia.